Research

Catenin contributions in cell and developmental biology.

All catenins with one exception share homology with the best-known family member, beta-catenin, and each catenin acts in a number of cell compartments. If we first consider the nucleus, beta-catenin binds to transcription factors such as TCF/ LEF in response to Wnt signals, leading to gene-target activation. We have revealed that less-understood catenins - our primary interest - likewise bind to key known or novel transcriptional complexes. For example, p120-catenin regulates genes that are instrumental in development and cancer, and we find that similar upstream controls act upon p120-isoform1 as beta-catenin. We also uncovered novel transcriptional complexes involving plakophilin3-catenin, delta-catenin, and p120-catenin, with the latter potentially involved in neural stemness versus differentiation decisions. Our current work upon delta-catenin instead centers on its actions outside the nucleus. We find that delta-catenin contains a phospho-switch at its C-terminus that “decides” between delta’s binding of one of two novel scaffolding proteins in neurons. We postulate that each outcome differentially alters the cytoskeleton to favor either dendrite elongation versus branching. Given the need to regulate neural connectivity (e.g. interactions of dendrites with axons), this key decision process must be properly executed countless times during the formation of the nervous system, and it is altered in prominent neurologic pathologies. In the longer term, we aspire to address the extent to which the functions of catenins are networked to meet an array of cellular and developmental goals.

A frog tadpole (Xenopus laevis), that exhibits a duplicate dorsal axis - hence there are two heads. The secondary axis was generated by the ectopic ventral expression of beta-catenin at an early embryonic stage. The experiment demonstrates the power of the Wnt signaling pathway in developmental systems (and cancer).